Modeling of molecular interaction between catechol and tyrosinase by DFT

• Published in: Journal of molecular structure 2020-02, Vol.1202, p.127192, Article 127192
• Main Authors: Polatoğlu, İlker, Karataş, Deniz
• Format: Article
• Language: English
• Subjects: Catechol; DFT; Modelling; Molecular interaction; Solvent; tyrosinase
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2019.127192

In this study, the synthetic active site model of tyrosinase enzyme’s “(His3)Cu..OH..Cu(His3) arrangement” is constituted by applying the density functional theory (DFT) to reveal the enzymatic conversion of catechol in molecular basis. This is the first time the binding mechanisms of catechol in relation to the enzyme active site (met-tyrosinase) in a vacuum environment, explicit water, and solvent (ethanol, acetone)/water mixture have been studied using the DFT. The theoretical results are supported along with the experimental ones to clarify the structure–activity relationship in these models. As understood from the mechanisms, the initial H abstraction from catechol is the most probable rate-limiting step. The parameters that cause the copper region to become congested or comfortable for H abstraction, such as the ordered structure of water molecules, Cu–Cu distance, H-bond distance, orientation and conformation of histidine residues around the copper center, and electrostatic potential of the system, play a significant role in the catechol/met-tyrosinase interaction. [Display omitted] •The molecular interaction between catechol and met-tyrosinase in four different models was revealed by applying DFT.•The structure–activity relationship was supported by experimental results.•Initial H abstraction from catechol is the most probable rate-limiting step.•Ethanol significantly enhanced the molecular interaction between catechol and met-tyrosinase.•Enzymatic reaction was retarded in the acetone environment.